20345-61-3Relevant articles and documents
Cyclobutanone mimics of penicillins: Effects of substitution on conformation and hemiketal stability
Johnson, Jarrod W.,Evanoff, Darryl P.,Savard, Marc E.,Lange, Gerald,Ramadhar, Timothy R.,Assoud, Abdeljalil,Taylor, Nicholas J.,Dmitrienko, Gary I.
, p. 6970 - 6982 (2008)
(Chemical Equation Presented) The tendency for carbocyclic analogues of penicillins to undergo hydrate and hemiketal formation is central to their ability to function as β-lactamase inhibitors. 2-Thiabicyclo[3.2.0]heptan- 6-one-4-carboxylates with alkoxy functionality at C3 have been prepared through two complementary diastereoselective substitution reactions following a highly stereoselective chlorination with sulfuryl chloride. We have found that carbocyclic analogues with 3β substituents favor an endo envelope conformation in solution, the solid state, and the gas phase, whereas those with 3α substituents adopt an exo envelope. Evidence from X-ray crystal structures and ab initio calculations suggests that an anomeric effect contributes to the large conformational preference of the tetrahydrothiophene ring that favors the C3 substituent in an axial orientation. In addition, the envelope conformation of the bicycle, which is determined by the stereochemistry of the C3 substituent, has a dramatic effect on the ability of the cyclobutanone to undergo hemiketal formation in methanol-d4.
Synthesis of a novel thiabicyclo[3.2.0]heptan-6-one analogue of penicillin
Martyres, Domnic H,Baldwin, Jack E,Adlington, Robert M,Lee, Victor,Probert, Mike R,Watkin, David J
, p. 4999 - 5007 (2001)
Synthesis of (1SR, 4SR, 5SR, 7RS)-7-(tert-butoxycarbonylamino)-2-thiabicyclo[3.2.0]heptan-6-one-4- carboxylic acid ethyl ester, a novel cyclobutanone analogue of a β-lactam antibiotic is described. This was achieved by [2+2] cycloaddition of a 2,3-dihydrothiophene with dichloroketene, followed by conversion to a cyclobutanol and use of an intramolecular nitrene insertion strategy to install nitrogen functionality at C-7 with endo stereochemistry.
Refining the structure?activity relationships of 2-phenylcyclopropane carboxylic acids as inhibitors of O-acetylserine sulfhydrylase isoforms
Magalh?es, Joana,Franko, Nina,Annunziato, Giannamaria,Pieroni, Marco,Benoni, Roberto,Nikitjuka, Anna,Mozzarelli, Andrea,Bettati, Stefano,Karawajczyk, Anna,Jirgensons, Aigars,Campanini, Barbara,Costantino, Gabriele
, p. 31 - 43 (2018/11/01)
The lack of efficacy of current antibacterials to treat multidrug resistant bacteria poses a life-threatening alarm. In order to develop enhancers of the antibacterial activity, we carried out a medicinal chemistry campaign aiming to develop inhibitors of
Stereoisomers of oseltamivir-synthesis, in silico prediction and biological evaluation
Hajzer, Viktória,Fi?era, Roman,Latika, Attila,Durmis, Július,Kollár, Jakub,Frecer, Vladimír,Tu?eková, Zuzana,Miertu?, Stanislav,Kostolansky, Franti?ek,Vare?ková, Eva,?ebesta, Radovan
, p. 1828 - 1841 (2017/03/09)
Oseltamivir is an important antiviral drug, which possess three chirality centers in its structure. From eight possible stereoisomers, only two have been synthesized and evaluated so far. We describe herein the stereoselective synthesis, computational activity prediction and biological testing of another three diastereoisomers of oseltamivir. These isomers have been synthesized using stereoselective organocatalytic Michael addition, cyclization and reduction. Their binding to viral neuraminidase N1 of influenza A virus was evaluated by quantum-chemical calculations and their anti-influenza activities were tested by an in vitro virus-inhibition assay. All three isomers displayed antiviral activity lower than that of oseltamivir, however, one of the stereoisomers, (3S,4R,5S)-isomer, of oseltamivir showed in vitro potency towards the Tamiflu-sensitive influenza viral strain A/Perth/265/2009(H5N1) comparable to Tamiflu.
PAIN RELIEF COMPOUNDS
-
Paragraph 0482, (2015/02/19)
The present invention relates to the use of compounds for the treatment or prevention of pain in mammals, in particularly in human beings, and also to a process for preparing these compounds.
Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel
Rodrigues, Nuno,Bennis, Khalil,Vivier, Delphine,Pereira, Vanessa,Chatelain, Franck C.,Chapuy, Eric,Deokar, Hemantkumar,Busserolles, Jér?me,Lesage, Florian,Eschalier, Alain,Ducki, Sylvie
supporting information, p. 391 - 402 (2014/03/21)
The TWIK-related K+ channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs. It has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to painful stimuli, suggesting that activation of TREK-1 could result in pain inhibition. Here we report the synthesis of a series of substituted caffeate esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-α-cyanocinnamate). These analogs were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid induced-writhing assay) leading to the identification a series of novel molecules able to activate TREK-1 and displaying potent analgesic activity in vivo.
N-heterocyclic carbene catalyzed umpolung of Michael acceptors for intermolecular reactions
Biju, Akkattu T.,Padmanaban, Mohan,Wurz, Nathalie E.,Glorius, Frank
supporting information; experimental part, p. 8412 - 8415 (2011/10/31)
leahciM! The N-heterocyclic carbene catalyzed umpolung of Michael acceptors proceeds through the formation of a deoxy-Breslow intermediate (see scheme; EWG=electron-withdrawing group). This nucleophilic species can react with other Michael acceptors in an intermolecular fashion, thereby resulting in the formation of homo- or heterodimeric olefins. This "Michael umpolung" should become a valuable method for the formation of densely functionalized olefins.
Investigation on lewis acid mediated diels-alder reactions of 2-phosphono-2-alkenoates. Application to total synthesis of (±)-α- alasken-8-one via reductive alkylation of resulting adduct
Liao, Chuan-Cheng,Zhu, Jia-Liang
body text, p. 7873 - 7884 (2010/01/16)
(Chemical Equation Presented) The Lewis acid mediated Diels-Alder reactions of three 2-phosphono-2-alkenoates including triethyl 2-phosphonoacrylate (1), triethyl 2-phosphonobut-2-enoate (2), and ethyl 2-(diethoxyphosphono)-3- methylbut-2-enoate (3) have been investigated. Of several Lewis acids tested, tin(IV) chloride was shown to be the most effective at enhancing the regio- and stereoselectivity of the reactions of 1 with the electron-rich dienes to result in the formation of the single regio- and/or stereoisomers in good yields. Bearing the β methyl group(s), 2 displayedmuch less reactivity than 1 while 3 was completely unreactive under the study's conditions. Throughout the investigation, we found that the cycloadditions of 2, especially of the Z-isomer, could be efficiently induced by using zinc chloride at elevated temperatures. Furthermore, a lithium naphthalenide (LN)-induced reductive alkylation process was applied to the resulting Diels-Alder adducts 4 to allow the phosphono group at the quaternary carbon centers to be replaced by various alkyl groups to afford the alkyl-substituted esters 12, therefore practically turning 1 and 2 into the useful synthetic equivalents of the corresponding 2-alkyl 2-alkenoates that usually display poor Diels-Alder reactivity. Application of this combined operation has facilitated the total synthesis of the sesquiterpene natural product α-alasken-8-one (8) in racemic form.
An approach to amino ester subunits of tamiflu
Kraus, George A.,Goronga, Tinopiwa
, p. 1765 - 1767 (2008/02/10)
A two-step synthesis of amino cyclohexene carboxylic acid esters has been achieved in good overall yield from nitro phosphonate and unsaturated aldehydes. Georg Thieme Verlag Stuttgart.
2-Diethoxyphosphoryl-4-nitroalkanoates - Versatile intermediates in the synthesis of α-alkylidene-γ-lactones and lactams
B?aszczyk, Edyta,Krawczyk, Henryk,Janecki, Tomasz
, p. 2685 - 2688 (2007/10/03)
Michael addition of various nitroalkanes 7a-f to ethyl (2- diethoxyphosphoryl)acrylate (6) gave 2-diethoxyphosphoryl-4-nitroalkanoates 8a-f. Transformation of the nitro functionality into hydroxy or amino group and cyclization yielded 3-(diethoxyphosphory
